Rare disorders that are associated with an increased thrombotic risk include the antiphospholipid antibody syndromes (APS), heparin-induced thrombocytopenia (HIT), combined thrombophilic states, paroxysmal nocturnal hemoglobinuria, thrombotic thrombocytopenic purpura, and the catastrophic 'thrombotic storm'. These disorders frequently exhibit more "aggressive" clinical phenotypes, affecting arterial, venous, and/or microvascular beds. Diagnostic and/or therapeutic limitations exist for each of these disorders, and prospective studies are needed to more clearly define the syndromes and develop better therapies. This application is for a multi-institutional academic center that focuses on rare thrombotic disorders, which will be developed through the following Aims: (1) Establish a Rare Disease Clinical Research Center focused on rare thrombotic disorders. Investigators from four academic centers will bring together existing registries (e.g., Antiphospholipid Syndrome Collaborative Registry) and programs (e.g., CDC-sponsored Thrombophilia Programs; Duke Center for Human Genetics) to identify and enroll patients into hypothesis-driven prospective clinical trials that focus on: . Genetic analysis of familial APS, familial APS/autoimmunity syndromes, and patients with catastrophic "thrombotic storm". . Identify risk factors for thrombosis in patients with antiphospholipid antibodies and HIT. . Define the natural history of patients with elevated hepadn-platelet factor 4 antibodies after bypass. Emerging opportunities from ongoing studies will be identified that promote new research directions, projects, and translational activities that foster links between the Center and industry. (2) Develop a training program for new investigators who are interested in rare thrombotic disorders. A program will be instituted that combines opportunities in clinical management as well as epidemiologic, genetic, diagnostic, and therapeutic investigations involving patients with rare thrombotic disorders. (3) Develop a web site that promotes education and research activities involving patients with rare thrombotic disorders. The web-site will be developed with the Data Technology and Coordinating Center and other Rare Disease Research Centers and will be for patients, healthcare providers, and the general public.